20-13785088-T-A

Variant names:

• chr20-13785088-T-A
• NM_024120.5:c.20T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024120.5(NDUFAF5):​c.20T>A​(p.Leu7His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NDUFAF5 NM_024120.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.986

Genes affected

NDUFAF5 (HGNC:15899): (NADH:ubiquinone oxidoreductase complex assembly factor 5) The NADH-ubiquinone oxidoreductase complex (complex I) of the mitochondrial respiratory chain catalyzes the transfer of electrons from NADH to ubiquinone, and consists of at least 43 subunits. The complex is located in the inner mitochondrial membrane. This gene encodes a mitochondrial protein that is associated with the matrix face of the mitochondrial inner membrane and is required for complex I assembly. A mutation in this gene results in mitochondrial complex I deficiency. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

ESF1 (HGNC:15898): (ESF1 nucleolar pre-rRNA processing protein homolog) Enables RNA binding activity. Predicted to be involved in rRNA processing. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1181981).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFAF5	NM_024120.5	c.20T>A	p.Leu7His	missense_variant	Exon 1 of 11	ENST00000378106.10	NP_077025.2
ESF1	NM_001276380.2	c.-252A>T		upstream_gene_variant		ENST00000617257.2	NP_001263309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFAF5	ENST00000378106.10	c.20T>A	p.Leu7His	missense_variant	Exon 1 of 11	1	NM_024120.5	ENSP00000367346.5
ESF1	ENST00000617257.2	c.-252A>T		upstream_gene_variant		5	NM_001276380.2	ENSP00000480783.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460368 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726510

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.057	T;.
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.43	T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.10
Sift	Benign	0.083	T;D
Sift4G	Benign	0.21	T;T
Polyphen		0.0010	B;B
Vest4		0.38
MutPred		0.25		Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP		0.34
MPC		0.29
ClinPred		0.087	T
GERP RS		0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.14
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-13765734;